Shiro Imokawa

Alterations in Smoking Habits Are Associated With Acute Eosinophilic Pneumonia

BACKGROUND Acute eosinophilic pneumonia (AEP) is characterized by a febrile illness, diffuse pulmonary infiltrates, and pulmonary eosinophilia. The etiology of AEP remains unknown, but several studies have proposed a relationship between cigarette smoking and AEP. However, most studies showing this possibility are single-case reports, and cigarette smoke has not been fully validated as a causative agent of AEP in a large series of patients. The present study was conducted to clarify the etiologic role of cigarette smoking in AEP, with special reference to alterations in smoking habits. METHODS We took a detailed history of smoking habits before AEP onset in 33 patients with AEP, and performed a cigarette smoke provocation test. RESULTS Of our AEP patients, all but one (97%) were current smokers. Interestingly, 21 of these were new-onset smokers, and 2 had restarted smoking after a 1- to 2-year cessation of smoking. The duration between starting smoking and AEP onset was within 1 month (0.67 +/- 0.53 months). Additionally, six of the remaining smokers had increased the quantity of cigarettes smoked daily, fourfold to fivefold, mostly within the month before AEP onset (0.81 +/- 0.58 months). Only three smokers had not changed their smoking habits before AEP onset. Cigarette smoke provocation tests revealed positive results in all nine patients tested. CONCLUSION These data suggest that recent alterations in smoking habits, not only beginning to smoke, but also restarting to smoke and increasing daily smoking doses, are associated with the development of AEP.

Rheumatoid lung disease: Prognostic analysis of 54 biopsy-proven cases

OBJECTIVE To investigate the prognostic significance of histopathological characteristics in patients with biopsy-proven rheumatoid lung disease (RLD). MATERIALS AND METHODS Retrospective analysis was conducted on samples from 54 RLD patients who underwent surgical lung biopsies (SLBs) at Hamamatsu University Hospital and affiliated hospitals between 1980 and 2009. The overall survival rate, the spectrum of histopathological diagnosis and their associated prognostic significance were investigated. RESULTS The study group consisted of 30 men and 24 women with a median age of 60.3 years. Histopathological analysis revealed the following: usual interstitial pneumonia (UIP), 15 cases; nonspecific interstitial pneumonia/fibrosis, 16 cases; organizing pneumonia, 4 cases; unclassifiable, 2 cases; desquamative interstitial pneumonia, 1 case; and bronchiolar disease, 16 cases. In survival outcome, 10 yr survival rate was 76.6%. Patients with UIP had significantly worse prognosis than those with non-UIP (RLD cases except those with UIP) (p = 0.0452). CONCLUSION RLD includes several histopathological groups. Patients with UIP have worse survival than those with other types of RLD. Histopathological diagnosis may have a major impact on prognostication in patients with RLD.

Distinct prognosis of idiopathic nonspecific interstitial pneumonia (NSIP) fulfilling criteria for undifferentiated connective tissue disease (UCTD)

BACKGROUND Although idiopathic nonspecific interstitial pneumonia (NSIP) was initially identified as a provisional diagnosis, the 2008 American Thoracic Society Project concluded that idiopathic NSIP is a distinct form of idiopathic interstitial pneumonia. However, an association between idiopathic NSIP and autoimmune diseases still attracts interest. In this context, a recent study proposed an intriguing concept that idiopathic NSIP is the pulmonary manifestation of undifferentiated connective tissue disease (UCTD). However, this has not been confirmed in a large number of patients with idiopathic NSIP. The present study was conducted to investigate the proportion and characteristics of patients with idiopathic NSIP who meet the criteria for UCTD. METHODS We reviewed 47 consecutive patients with idiopathic NSIP and examined whether they met prespecified criteria for UCTD. Furthermore, we compared the clinical characteristics between patients fulfilling the UCTD criteria (UCTD-NSIP) and those not meeting them (Non-UCTD-NSIP). RESULTS Of 47 patients with idiopathic NSIP, 22 (47%) met the UCTD criteria. Common symptoms associated with connective tissue diseases (CTDs) were skin change (50%) and Raynauds phenomenon (41%) in UCTD-NSIP. UCTD-NSIP showed a female predominance and significantly higher percentages of lymphocytes with a lower CD4/CD8 ratio in bronchoalveolar lavage than Non-UCTD-NSIP. Interestingly, UCTD-NSIP had a significantly better survival than Non-UCTD-NSIP. CONCLUSIONS Idiopathic NSIP included subjects who fulfilled the UCTD criteria, and these subjects had different clinical characteristics with significantly better outcome than those who did not meet the criteria. These data suggest that a part, but not all, of patients with idiopathic NSIP show CTD-like features with a distinct prognosis.

Clinicopathological features of chronic hypersensitivity pneumonitis

Objective: Only limited information exists concerning the clinical and pathological features of chronic hypersensitivity pneumonitis (HP) in Japan and elsewhere. We present data on clinicopathological features of chronic HP obtained through a Japanese nationwide survey.

Possible Involvement of an Environmental Agent in the Development of Acute Eosinophilic Pneumonia

BACKGROUND Although the pathogenesis of acute eosinophilic pneumonia remains largely unknown, it has been suggested that it may include a hypersensitivity phenomenon induced by inhaled environmental antigens. METHODS To investigate this possibility, we studied the effect of environmental challenges in three patients with acute eosinophilic pneumonia. Symptoms and laboratory findings were evaluated before and after the challenge tests in the patients homes and their places of work. RESULTS After the provocation challenges to their homes, all three patients developed fever, cough, and fatigue and two of them presented with dyspnea. Inspiratory crackles became audible in all cases, and there was a decreased Pao2 level in two. Similar challenges at their workplaces were negative. After moving out of their homes, the patients engaged in their usual work but had no recurrent episodes. CONCLUSIONS These results suggest that environmental factors in the home can be the cause of acute eosinophilic pneumonia. In order to elucidate the pathogenesis of the disease, it is important to further investigate environmental factors.

Amount of elastic fibers predicts prognosis of idiopathic pulmonary fibrosis

BACKGROUND Elastic fibers enhance the stiffness of fibrotic tissues, but their role in the pathophysiology of idiopathic pulmonary fibrosis (IPF) has not been fully examined. The aim of this study was to determine clinical significance of the amount of elastic fibers in IPF. METHODS We studied the surgical lung biopsy specimens of 43 patients with IPF. Histological specimens were stained using the Elastica Van Gieson method and digital images were taken. The number of pixels containing elastic fibers was divided by the number occupied by fibrotic tissue, from which the proportion of elastic fibers (elastic fiber score, %) was calculated. The relationships between the elastic fiber score and clinical, radiological and pathological findings, and prognosis were explored. RESULTS The median elastic fiber score was 10.9% (range 5.1-23.3%). Scores were inversely correlated with % predicted forced vital capacity (r -0.451, p-value 0.003) and positively correlated with decline in forced vital capacity over 12 months (r -0.475, p-value 0.033). Furthermore, elastic fiber score correlated with the extent of fibrotic lesions assessed on high resolution computed tomography as well as the degree of collagen deposition on biopsy specimens. Patients with high elastic fiber scores had significantly worse outcomes than those with low scores (5-year survival rate was 48.7% and 84.0%, respectively, p-value 0.024), and elastic fiber score was an independent predictor of poor prognosis (hazard ratio 1.21, p-value 0.005). CONCLUSION The amount of elastic fiber in fibrotic tissue is a prognostic indicator in patients with IPF.

Maintenance therapy with pemetrexed and bevacizumab versus pemetrexed monotherapy after induction therapy with carboplatin, pemetrexed, and bevacizumab in patients with advanced non-squamous non small cell lung cancer

OBJECTIVES Single agent maintenance therapy is widely accepted for advanced non-squamous non small cell lung cancer (NSCLC). However, there is no consensus on the initial and maintenance phase regimens, and the clinical benefit of adding bevacizumab to cytotoxic drugs in the maintenance phase remains unclear. METHODS Chemotherapy-naïve patients with non-squamous NSCLC were randomly assigned to maintenance therapy with pemetrexed and bevacizumab or pemetrexed alone, after achieving disease control after four cycles of induction therapy with carboplatin (area under the curve = 6), pemetrexed (500 mg/m(2)), and bevacizumab (15 mg/kg). The primary end-point was 1-year progression-free survival (PFS) rate. RESULTS One hundred ten patients were enrolled in the study, with 55 patients assigned to the two groups. The mean 1-year PFS rate was 43.9% (95% confidence interval [CI]: 29.6-59.2%) in the combination maintenance group and 35.2% (95% CI: 22.1-51.0%) in the pemetrexed maintenance group, and the difference was not significant (p = 0.433). Median PFS measured from enrolment was 11.5 months (95% CI: 7.1-19.0) in the combination maintenance group and 7.3 months (95% CI: 5.7-14.1, hazard ratio: 0.73, 95% CI: 0.44-1.19, log-rank p = 0.198) in the pemetrexed maintenance group. Nasal haemorrhage, hypertension, and proteinuria were significantly more frequent in the combination maintenance group, but they were mild and tolerable. CONCLUSION Both maintenance therapy with pemetrexed alone and pemetrexed and bevacizumab in combination were feasible in patients with non-squamous NSCLC who have achieved disease control after induction therapy with carboplatin, pemetrexed, and bevacizumab. According to the selection design, differences in the superiority between these maintenance therapies were not demonstrated.

Nonspecific interstitial pneumonia: Prognostic significance of high-resolution computed tomography in 59 patients

Objective: To retrospectively analyze the prognostic implications of high-resolution computed tomography (HRCT) findings for patients with biopsy-proven nonspecific interstitial pneumonia (NSIP). Methods: Fifty-nine patients with NSIP (25 idiopathic NSIP, 34 collagen-vascular disease-associated NSIP) were included. Two chest radiologists independently evaluated the extent, presence, and distribution of various HRCT findings. Cox hazards analysis was used to evaluate the relationship between HRCT findings and prognosis. Results: The 5-year survival rate was 83% and the 10-year survival rate was 66%. Univariate analysis revealed that the extent of areas with ground-glass attenuation without traction bronchi-bronchiolectasis and that of airs-pace consolidation were associated with favorable outcome, whereas that of intralobular reticular opacities was associated with worse prognosis. Multivariate analysis showed that the extent of air-space consolidation was an independent factor of favorable outcome. Conclusion: In NSIP, the extent of areas with ground-glass attenuation without traction bronchi-bronchiolectasis, air-space consolidation, and intralobular reticular opacities correlate with survival.

Evaluation of palonosetron and dexamethasone with or without aprepitant to prevent carboplatin-induced nausea and vomiting in patients with advanced non-small-cell lung cancer.

OBJECTIVES Although antiemetic management has improved, better control of chemotherapy-induced nausea and vomiting (CINV), particularly during the delayed phase, is needed. The benefit of combination therapy using dexamethasone and the second-generation 5-hydroxytryptamine-3 receptor antagonist palonosetron compared with that of other such receptor antagonists in carboplatin-based chemotherapy is unclear. The effectiveness of adding aprepitant for CINV treatment in moderate emetogenic chemotherapy is also unknown. We compared the efficacy and safety of triple antiemetic therapy using aprepitant, palonosetron, and dexamethasone with that of double antiemetic therapy using palonosetron and dexamethasone in patients with advanced non-small-cell lung cancer receiving carboplatin-containing chemotherapy. METHODS Chemotherapy-naïve patients with non-small-cell lung cancer were enrolled in this prospective controlled study. Eighty patients were randomly assigned to groups receiving either double antiemetic therapy with palonosetron and dexamethasone, or triple antiemetic therapy with aprepitant, palonosetron, and dexamethasone. Complete response rate (no vomiting episode and no rescue therapy) was evaluated as the primary endpoint during the 5-day post-chemotherapy period. RESULTS The aprepitant add-on and double therapy groups showed overall complete response rates of 80.5% (95% confidence interval [CI]: 68.4-92.6%) and 76.9% (95% CI: 63.7-90.1%; odds ratio [OR]: 0.81; 95% CI; 0.27-2.36; p=0.788), respectively. Complete responses in the acute and delayed phases and overall incidences of treatment-related adverse events were similar between groups. CONCLUSION According to the selection design, triple antiemetic therapy with aprepitant, palonosetron, and dexamethasone was not considered as an option for further studies.

Pulmonary Metastasis from Urothelial Carcinoma Showing Progressive Multiple Cystic Lesions

Multiple thin-walled cystic lesions in the lung can reflect a variety of diseases (Table E1 in the online supplement), such as lymphangioleiomyomatosis, pulmonary Langerhans’ cell histiocytosis, Birt-Hogg-Dubé syndrome, lymphoid interstitial pneumonia, alveolar septal amyloidosis, and cystic pneumocystis pneumonia (1–4). Bronchioloalveolar carcinoma (5, 6), pulmonary metastasis of sarcomas (7, 8), and meningioma (9) are also reported, but they are extremely rare. We herein describe a patient with pulmonary metastasis from urothelial carcinoma of the urinary bladder presenting as multiple thin-walled cystic lesions on computed tomography (CT), which is an uncommon manifestation. A 76-year-old man with a smoking history of 50 pack-years was admitted to our hospital for the sudden onset of dyspnea. Six months earlier, he had undergone transurethral resection of a bladder tumor with the diagnosis of high-grade urothelial carcinoma. Radical cystectomy and bilateral distal ureterectomy with creation of a ureter–skin conduit were performed. A chest X-ray on admission showed bilateral pneumothoraces, which required placement of chest tubes bilaterally. Chest CT performed after reexpansion revealed multiple thin-, smooth-walled cysts measuring up to 1.5 cm in diameter (Figure 1B). No other types of pulmonary lesions, such as nodules or cavitary lesions with thick or irregular walls, were found; however, some of the pulmonary arteries were dilated. These findings had not been detected on chest CT scans taken 4 months earlier (Figure 1A). Pleurodesis was performed on the left side, which prevented air leakage. Because of the recurrence of right pneumothorax, the patient underwent thoracoscopy with right upper and lower lobe wedge resections and pleurodesis. The macroscopic features of the cystic lesion were consistent with a pulmonary bulla. The walls of the cysts lacked a lining epithelium and comprised a dense proliferation of tumor cells (Figure E1a). The histological findings closely resembled those of the previously resected bladder tumor, and a diagnosis of metastatic urothelial carcinoma was made. Around the cysts, tumor cells extended along the alveolar walls, and some alveoli were distended (Figure E1b). Some terminal bronchioles were invaded and narrowed by tumor growth (Figure E1c). Tumor emboli in the pulmonary arteries and capillaries were also noted (Figures E1c and E1d). The patient’s general condition worsened with the progression of bladder carcinoma. Serial CT scans demonstrated progression and marked enlargement of the cystic lesions (Figure 1C). He deteriorated and died 2 months after the diagnosis of his pulmonary complications. The lung is one of themost common sites of distant metastasis from bladder cancer (10, 11). Usual patterns of pulmonary involvement include multiple nodules, a solitary mass, or interstitial micronodules (2, 10, 11), but it rarely manifests as cavitary pulmonary lesions with thick, irregular walls (12–15). The present case is unusual in that the cystic metastasis had thin, smooth-walled bulla-like features. Metastatic soft tissue sarcomas (7, 8) or primary bronchioloalveolar carcinoma (5, 6) may show the same pattern, but this has not previously been reported in metastatic urothelial carcinoma.